The major goal of this project is a basic understanding of the biological and biochemical basis of Fv-1 restriction, a naturally occurring cellular system which inhibits the replication of specific N-or B-tropic mouse leukemia viruses. The studies primarily involve a variety of cell culture techniques for quantitation of virus replication and transformation. Current studies emphasize the use of tropic MSV pseudotypes to study Fv-1 restriction independently of MuLV replication. The Fv-1 related restriction of N-tropic MuLV observed in infectivity studies using Balb/3T3 cells is a result of the requirement for infection with two N-tropic MuLV particles in order for viral replication to take place. The two particles, although identical, have different functions. One particle abrogates Fv-1 restriction in a Balb/3T3 cell rendering it permissive for a period of about 24 hours to productive infection with a second N-tropic MuLV virus. Quantitative inactivation studies with gamma irradiation and heat indicate that an MuLV particle need not be infectious in order to abrogate Fv-1 restriction. BIBLIOGRAPHIC REFERENCES: Rein, A., Kashmiri, S. V. S., Bassin, R. H., Gerwin, B. I. and Duran-Troise, G.: Studies on the mechanism of Fv-1 restriction: Properties of determinants specifying viral tropism. In Animal Virology, D. Baltimore, A. S. Huang and C. F. Fox, (eds.) ICN-UCLA Symposium on Molecular and Cellular Biology IV, 269-282, 1976. Duran-Troise, G., Bassin, R. H., Rein, A. and Gerwin, B. I.: Loss of Fv-1 restriction in Balb/3T3 cells following infection with a single N-tropic murine leukemia virus particle. Cell 10: 479-488, 1977.